Extended-spectrum antiprotozoal bumped kinase inhibitors: A review

Wesley C. Van Voorhis, J. Stone Doggett, Marilyn Parsons, Matthew A. Hulverson, Ryan Choi, Samuel Arnold, Michael W. Riggs, Andrew Hemphill, Daniel K. Howe, Robert H. Mealey, Audrey O T Lau, Ethan A. Merritt, Dustin J. Maly, Erkang Fan, Kayode K. Ojo

Research output: Research - peer-reviewArticle

  • 2 Citations

Abstract

Many life-cycle processes in parasites are regulated by protein phosphorylation. Hence, disruption of essential protein kinase function has been explored for therapy of parasitic diseases. However, the difficulty of inhibiting parasite protein kinases to the exclusion of host orthologues poses a practical challenge. A possible path around this difficulty is the use of bumped kinase inhibitors for targeting calcium dependent protein kinases that contain atypically small gatekeeper residues and are crucial for pathogenic apicomplexan parasites' survival and proliferation. In this review, we review efficacy against the kinase target, the parasite growth in vitro, and in animal infection models, as well as the relevant pharmacokinetic and safety parameters of bumped-kinase inhibitors.

LanguageEnglish (US)
JournalExperimental Parasitology
DOIs
StateAccepted/In press - 2017

Fingerprint

Parasites
Phosphotransferases
Protein Kinases
Parasitic Diseases
Life Cycle Stages
Animal Models
Pharmacokinetics
Phosphorylation
Safety
Growth
Infection
Proteins
Therapeutics
calcium-dependent protein kinase
In Vitro Techniques

Keywords

  • Bumped-kinase inhibitors
  • Calcium-dependent protein kinase
  • Gatekeeper residue

ASJC Scopus subject areas

  • Parasitology
  • Immunology

Cite this

Van Voorhis, W. C., Doggett, J. S., Parsons, M., Hulverson, M. A., Choi, R., Arnold, S., ... Ojo, K. K. (2017). Extended-spectrum antiprotozoal bumped kinase inhibitors: A review. Experimental Parasitology. DOI: 10.1016/j.exppara.2017.01.001

Extended-spectrum antiprotozoal bumped kinase inhibitors : A review. / Van Voorhis, Wesley C.; Doggett, J. Stone; Parsons, Marilyn; Hulverson, Matthew A.; Choi, Ryan; Arnold, Samuel; Riggs, Michael W.; Hemphill, Andrew; Howe, Daniel K.; Mealey, Robert H.; Lau, Audrey O T; Merritt, Ethan A.; Maly, Dustin J.; Fan, Erkang; Ojo, Kayode K.

In: Experimental Parasitology, 2017.

Research output: Research - peer-reviewArticle

Van Voorhis, WC, Doggett, JS, Parsons, M, Hulverson, MA, Choi, R, Arnold, S, Riggs, MW, Hemphill, A, Howe, DK, Mealey, RH, Lau, AOT, Merritt, EA, Maly, DJ, Fan, E & Ojo, KK 2017, 'Extended-spectrum antiprotozoal bumped kinase inhibitors: A review' Experimental Parasitology. DOI: 10.1016/j.exppara.2017.01.001
Van Voorhis WC, Doggett JS, Parsons M, Hulverson MA, Choi R, Arnold S et al. Extended-spectrum antiprotozoal bumped kinase inhibitors: A review. Experimental Parasitology. 2017. Available from, DOI: 10.1016/j.exppara.2017.01.001
Van Voorhis, Wesley C. ; Doggett, J. Stone ; Parsons, Marilyn ; Hulverson, Matthew A. ; Choi, Ryan ; Arnold, Samuel ; Riggs, Michael W. ; Hemphill, Andrew ; Howe, Daniel K. ; Mealey, Robert H. ; Lau, Audrey O T ; Merritt, Ethan A. ; Maly, Dustin J. ; Fan, Erkang ; Ojo, Kayode K./ Extended-spectrum antiprotozoal bumped kinase inhibitors : A review. In: Experimental Parasitology. 2017
@article{84001f5658824b54bd70b13e58e303fe,
title = "Extended-spectrum antiprotozoal bumped kinase inhibitors: A review",
abstract = "Many life-cycle processes in parasites are regulated by protein phosphorylation. Hence, disruption of essential protein kinase function has been explored for therapy of parasitic diseases. However, the difficulty of inhibiting parasite protein kinases to the exclusion of host orthologues poses a practical challenge. A possible path around this difficulty is the use of bumped kinase inhibitors for targeting calcium dependent protein kinases that contain atypically small gatekeeper residues and are crucial for pathogenic apicomplexan parasites' survival and proliferation. In this review, we review efficacy against the kinase target, the parasite growth in vitro, and in animal infection models, as well as the relevant pharmacokinetic and safety parameters of bumped-kinase inhibitors.",
keywords = "Bumped-kinase inhibitors, Calcium-dependent protein kinase, Gatekeeper residue",
author = "{Van Voorhis}, {Wesley C.} and Doggett, {J. Stone} and Marilyn Parsons and Hulverson, {Matthew A.} and Ryan Choi and Samuel Arnold and Riggs, {Michael W.} and Andrew Hemphill and Howe, {Daniel K.} and Mealey, {Robert H.} and Lau, {Audrey O T} and Merritt, {Ethan A.} and Maly, {Dustin J.} and Erkang Fan and Ojo, {Kayode K.}",
year = "2017",
doi = "10.1016/j.exppara.2017.01.001",
journal = "Experimental Parasitology",
issn = "0014-4894",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - Extended-spectrum antiprotozoal bumped kinase inhibitors

T2 - Experimental Parasitology

AU - Van Voorhis,Wesley C.

AU - Doggett,J. Stone

AU - Parsons,Marilyn

AU - Hulverson,Matthew A.

AU - Choi,Ryan

AU - Arnold,Samuel

AU - Riggs,Michael W.

AU - Hemphill,Andrew

AU - Howe,Daniel K.

AU - Mealey,Robert H.

AU - Lau,Audrey O T

AU - Merritt,Ethan A.

AU - Maly,Dustin J.

AU - Fan,Erkang

AU - Ojo,Kayode K.

PY - 2017

Y1 - 2017

N2 - Many life-cycle processes in parasites are regulated by protein phosphorylation. Hence, disruption of essential protein kinase function has been explored for therapy of parasitic diseases. However, the difficulty of inhibiting parasite protein kinases to the exclusion of host orthologues poses a practical challenge. A possible path around this difficulty is the use of bumped kinase inhibitors for targeting calcium dependent protein kinases that contain atypically small gatekeeper residues and are crucial for pathogenic apicomplexan parasites' survival and proliferation. In this review, we review efficacy against the kinase target, the parasite growth in vitro, and in animal infection models, as well as the relevant pharmacokinetic and safety parameters of bumped-kinase inhibitors.

AB - Many life-cycle processes in parasites are regulated by protein phosphorylation. Hence, disruption of essential protein kinase function has been explored for therapy of parasitic diseases. However, the difficulty of inhibiting parasite protein kinases to the exclusion of host orthologues poses a practical challenge. A possible path around this difficulty is the use of bumped kinase inhibitors for targeting calcium dependent protein kinases that contain atypically small gatekeeper residues and are crucial for pathogenic apicomplexan parasites' survival and proliferation. In this review, we review efficacy against the kinase target, the parasite growth in vitro, and in animal infection models, as well as the relevant pharmacokinetic and safety parameters of bumped-kinase inhibitors.

KW - Bumped-kinase inhibitors

KW - Calcium-dependent protein kinase

KW - Gatekeeper residue

UR - http://www.scopus.com/inward/record.url?scp=85010576763&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85010576763&partnerID=8YFLogxK

U2 - 10.1016/j.exppara.2017.01.001

DO - 10.1016/j.exppara.2017.01.001

M3 - Article

JO - Experimental Parasitology

JF - Experimental Parasitology

SN - 0014-4894

ER -